Role of proteases and their tissue inhibitors in pregnancy outcome

Abstract

Mammalian pregnancy is the successful outcome of series of events comprising of effective fertilization of male and female gamete, controlled growth and development of the embryo in the oviduct, transport to the uterus, attachment and implantation in the endometrium. These processes are coordinately and principally regulated by specific steroid hormones, cytokines and growth factors. Recently, matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) have been found to coordinate these events in major ways. They have been found to be involved in folliculogenesis, ovulation, corpus luteum turnover in ovary and degradation and regeneration uterine endometrium (known as endometrial tissue remodeling) during estrous cycle, implantation and placentation that are required for successful pregnancy outcome. The activities of these proteases and their inhibitors change dynamically to release healthy oocytes from ovary and during early pregnancy to render the uterine microenvironment suitable for attachment and implantation of growing embryo and to transform it in to a developed fetus through establishment of feto-maternal circulation. There exists a fine balance between the activities of these proteases and their inhibitors to regulate these events. Any breach in the equilibrium of the proteases and their inhibitors in the ovary or uterine microenvironment or in their regulation may pre-dispose a condition of failed pregnancy. An account of such proteases and their inhibitors and their role in pregnancy outcome has been discussed in this chapter.